Effect of ethacrynic acid on the thick ascending limb of Henle's loop

Abstract

Cortical thick ascending limbs of Henle's loop were dissected from rabbit kidneys and perfused in vitro. The diuretic ethacrynic acid (10-3M) in the tubule lumen caused a reversible decrease in the electrical potential difference (PD). Ethacrynic cysteine complex, a major urinary excretion product of ethacrynic acid, also caused a reversible decrease in the PD as well as in net chloride transport, but at a much lower concentration (3 x 10-6M) in the lumen. Ethacrynic cysteine in the bath (10-5M) had no effect on the PD. Ethacrynic cysteine had little effect on Na and Cl conductances, measured electrically. On the basis of these results it is suggested that the ethacrynic cysteine complex is the major active form of the drug in vivo and that it acts in the lumen of the thick ascending limb of Henle's loop to inhibit active Cl transport and thereby diminish NaCl reabsorption.